ArticleJournal of the American College of Cardiology2014
Genome editing of isogenic human induced pluripotent stem cells recapitulates long QT phenotype for drug testing.
Article in Journal of the American College of Cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 174 citations in OpenAlex.
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- Early Cytoskeletal Remodeling Drives Hypertrophic Cardiomyopathy Pathogenesis inJournal of cardiovascular development and disease · 2025Article
- Biomimetic Approaches in the Development of Optimised 3D Culture Environments for Drug Discovery in Cardiac Disease.Biomimetics (Basel, Switzerland) · 2025Review
- Bioengineering Approaches to In Vitro Modeling of Genetic and Acquired Cardiac Diseases.Current cardiology reports · 2025Review
- Optimizing approaches for targeted integration of transgenic cassettes by integrase-mediated cassette exchange in mouse and human stem cells.Stem cells (Dayton, Ohio) · 2025Article
- Applications, Limitations, and Considerations of Clinical Trials in a Dish.Bioengineering (Basel, Switzerland) · 2024Review
- Toward the latest advancements in cardiac regeneration using induced pluripotent stem cells (iPSCs) technology: approaches and challenges.Journal of translational medicine · 2024Review
- Using induced pluripotent stem cells for drug discovery in arrhythmias.Expert opinion on drug discovery · 2024Review
- Article
- Modeling mutation-specific arrhythmogenic phenotypes in isogenic human iPSC-derived cardiac tissues.Scientific reports · 2024Article
- Gene editing and reprogramming of human fibroblast cells (hFBs) to human pluripotent stem cells (hiPSCs).Neuromethods · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- The Advantages, Challenges, and Future of Human-Induced Pluripotent Stem Cell Lines in Type 2 Long QT Syndrome.Journal of cardiovascular translational research · 2023Review
- Gene Editing and Human iPSCs in Cardiovascular and Metabolic Diseases.Advances in experimental medicine and biology · 2023Article
- Genome Editing and Inherited Cardiac Arrhythmias.Advances in experimental medicine and biology · 2023Article
- Modeling long QT syndrome type 2 on-a-chip via in-depth assessment of isogenic gene-edited 3D cardiac tissues.Science advances · 2022Article
- Clinical Trial in a Dish for Space Radiation Countermeasure Discovery.Life sciences in space research · 2022Review
- Translational potential of hiPSCs in predictive modeling of heart development and disease.Birth defects research · 2022Review
- Modelling Diabetic Cardiomyopathy: Using Human Stem Cell-Derived Cardiomyocytes to Complement Animal Models.Metabolites · 2022Review
47 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundHuman induced pluripotent stem cells (iPSCs) play an important role in disease modeling and drug testing. However, the current methods are time-consuming and lack an isogenic control.
objectivesThis study sought to establish an efficient technology to generate human PSC-based disease models with isogenic control.
methodsThe ion channel genes KCNQ1 and KCNH2 with dominant negative mutations causing long QT syndrome types 1 and 2, respectively, were stably integrated into a safe harbor AAVS1 locus using zinc finger nuclease technology.
resultsPatch-clamp recording revealed that the edited iPSC-derived cardiomyocytes (iPSC-CMs) displayed characteristic long QT syndrome phenotype and significant prolongation of the action potential duration compared with the unedited control cells. Finally, addition of nifedipine (L-type calcium channel blocker) or pinacidil (KATP-channel opener) shortened the action potential duration of iPSC-CMs, confirming the validity of isogenic iPSC lines for drug testing in the future.
conclusionsOur study demonstrates that iPSC-CM-based disease models can be rapidly generated by overexpression of dominant negative gene mutants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.